Cell surface carbohydrates change during development suggesting that they are probably involved in differentiation. These developmentally-regulated changes allow some antibodies directed against carbohydrates to discriminate among tissues, both normal and malignant. To obtain cell-specific monoclonal antibodies, mice and rats have been immunized with various cell types in many laboratories. Some of the antibodies derived from spleen cells of the immunized animals that have an apparent specificity for certain cells and developmental stages are directed against carbohydrates. The structures of over 100 of these carbohydrate antigens have been elucidated. Most of them are related to the human ABO and Lewis blood group antigens. The antibodies are being used to study changes in cell surface carbohydrates during development in hopes of providing insights into the functions of glycoconjugates. For example, antibody LeoMel 3 which is directed against the ganglioside GD3, specifically inhibits killing of melanoma cells by human anomalous killer cells. These killer cells differentiate from classical cytotoxic T lymphocytes and lyse freshly isolated human melanoma cells which are insensitive to natural killer cell-mediated lysis. It is likely that the killer cells recognize the sugar sequence of ganglioside GD3. Antibody LeoMel 3 is an IgM. Other IgM antibodies from the same fusion that bind melanoma cells do not inhibit killer cell-mediated lysis. Another antibody, 18B8, which is directed against the ganglioside GT3, reacts only with the inner and outer synaptic layers of developing chick retina. It is possible that the sugar sequence of ganglioside GT3 is involved in synapse formation possibly by binding to lectin-like molecules on neuronal cell surfaces.